Follicle Stimulating Hormone Superagonists

Abstract

Modified VEGF proteins that inhibit VEGF-mediated activation or proliferation of endothelial cells are disclosed. The analogs may be used to inhibit VEGF-mediated activation of endothelial cells in angiogenesis-associated diseases such as cancer, inflammatory diseases, eye diseases, and skin disorders.

1 - 137 . (canceled) 
     
     
         138 . A method of inducing superovulation in an animal, comprising:
 administering an effective amount of a superactive follicle stimulating hormone (FSH) to the animal, wherein said superactive FSH comprises an alpha chain comprising basic amino acid substitutions at positions 18, 20 and 24; and the alpha chain further comprises an ANITV (SEQ ID NO: 3) N-terminal extension.   
     
     
         139 . The method of  claim 138 , wherein superovulation is characterized by an increase in oocyte number as compared to a like animal receiving the same amount of recombinant FSH. 
     
     
         140 . The method of  claim 139 , wherein the oocyte number increases at least about 10% as a result of administration of said superactive equine FSH at the maximally effective dose for oocyte number. 
     
     
         141 . The method of  claim 138 , wherein the alpha chain further comprises a basic amino acid substitution at position 17. 
     
     
         142 . The method of  claim 138 , wherein the basic amino acid is an arginine, a lysine, or a histidine, or a modification thereof. 
     
     
         143 . The method of  claim 138 , wherein the amino acid substitutions at positions 18, 20 and 24 are arginine substitutions. 
     
     
         144 . The method of  claim 141 , wherein the amino acid substitutions at positions 17, 18, 20 and 24 are arginine substitutions. 
     
     
         145 . The method of  claim 138 , wherein said ANTIV (SEQ ID NO: 3) extension prolongs the in vivo half life of the superactive FSH. 
     
     
         146 . The method of  claim 138 , wherein the superactive FSH is a bovine FSH further comprising a bovine beta subunit, and the animal is a cow. 
     
     
         147 . The method of  claim 144 , wherein the superactive FSH is a bovine FSH further comprising a bovine beta subunit, and the animal is a cow. 
     
     
         148 . The method of  claim 138 , wherein the superactive FSH is an equine FSH further comprising a equine beta subunit, and the animal is a horse. 
     
     
         149 . The method of  claim 143 , wherein the superactive FSH is an equine FSH further comprising a equine beta subunit, and the animal is a horse. 
     
     
         150 . The method of  claim 138 , wherein the superactive FSH is an ovine FSH further comprising a wild ovine beta subunit, and the animal is a sheep. 
     
     
         151 . The method of  claim 145 , wherein the superactive FSH is an ovine FSH further comprising a wild ovine beta subunit, and the animal is a sheep. 
     
     
         152 . The method of  claim 138 , wherein the superactive FSH is a porcine FSH further comprising a wild porcine beta subunit, and the animal is a pig. 
     
     
         153 . The method of  claim 144 , wherein the superactive FSH is a porcine FSH further comprising a wild porcine beta subunit, and the animal is a pig. 
     
     
         154 . The method of  claim 138 , wherein said superactive FSH is administered by injection. 
     
     
         155 . The method of  claim 138 , wherein the injection is intramuscular injection. 
     
     
         156 . The method of  claim 138 , wherein said superactive FSH is administered by ingestion.